Widespread implementation of prophylactic human papillomavirus (HPV) vaccines could substantially decrease morbidity and mortality from cervical cancer and other HPV-related diseases. Information about epidemiologic trends in HPV after vaccine introduction in community settings is essential in order to assess the progress and population impact of HPV immunization programs, and to provide data for programmatic and policy decisions. Thus, we conducted pilot HPV surveillance studies among ~800 13-26 year-old young women, before (2007; none vaccinated) and three years after (2010; 59% vaccinated) widespread vaccine introduction in a community. We found: 1) a substantial decline in vaccine-type HPV prevalence among all women (58%), 2) evidence for herd protection (i.e. a decline of 49% in vaccine-type HPV among unvaccinated women), and 3) possible evidence for type-replacement (i.e. an increase of 25% in the prevalence of non- vaccine-type HPV among vaccinated women). The overall objective of this proposal is to further characterize the community-level impact of HPV vaccine introduction, in men as well as women, by determining changes in vaccine-type HPV, characterizing herd protection, and investigating possible type replacement during the first nine years after HPV vaccine introduction. We will pursue the following three specific aims: (1) Determine trends in vaccine-type HPV prevalence among young women and men to a) assess the epidemiologic impact of HPV vaccine introduction in the community, and b) explore changes in the prevalence of genetically-related HPV types; (2) Determine trends in vaccine-type HPV prevalence among unvaccinated young women and men, in order to a) characterize and b) examine mechanisms for herd protection after vaccine introduction in the community; and (3) Determine trends in non-vaccine-type HPV prevalence among vaccinated and unvaccinated young women and men, in order to a) investigate and b) examine alternative (e.g. statistical) explanations for HPV type-replacement. We plan to accomplish the overall objective using the following approach: we will enroll diverse samples of 13-26 year-old women (N=400) and men (N=400) in two additional surveillance studies (total N=1600), and examine vaccination rates and HPV prevalence at all four time points in women (2007, 2010, 2013, and 2016) and two time points in men (2013 and 2016). The proposed research is innovative because 1) it is the first study to provide empirical data concerning changes in vaccine-type HPV, herd protection, and type replacement during the first nine years after HPV vaccine introduction in both men and women; 2) the data could shift current research and clinical practice paradigms in vaccine development; and 3) the research plan utilizes novel concepts, approaches and methodologies to explore mechanisms of herd protection and type-replacement. The proposed research is significant, because it will help to characterize the community-level impact of HPV immunization programs and provide data that are essential for programmatic and policy decisions to maximize the public health impact of HPV vaccination.